Ethyl Acetate → 5-Bromo-3-(trifluoromethyl)quinoline

HRID 2098037Notes

Reaction equation

HRID 2098037 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2.[Br:15]N1C(=O)CCC1=O.[OH-].[Na+].C(OCC)(=O)C>S(=O)(=O)(O)O.S([O-])([O-])=O.[Na+].[Na+]>[Br:15][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[CH:4][C:3]([C:2]([F:1])([F:13])[F:14])=[CH:12]2.[Br:15][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:11]=1[CH:12]=[C:3]([C:2]([F:1])([F:13])[F:14])[CH:4]=[N:5]2

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 67184N-bromobutanimideHCID 120251663-(Trifluoromethyl)quinoline

Product 2

HCID 469415118-Bromo-3-(trifluoromethyl)quinolineHCID 687590145-Bromo-3-(trifluoromethyl)quinolineYield 37%

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidSolventHCID 24437Sodium SulfiteSolvent

Procedure

3-(Trifluoromethyl)quinoline (7.00 g, 35.5 mmol) and N-bromosuccinimide (9.00 g, 50.6 mmol) in concentrated sulfuric acid (50 ml) was heated to 50° C. After stirring for 1.5 h, the solution was cooled to ambient temperature, diluted with saturated aq. sodium sulfite, made alkaline with 3 N aq. sodium hydroxide, and extracted with methylene chloride. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was flash chromatographed with 99:1, 49:1, 24:1, and 23:2 hexane:ethyl acetate as the eluant to afford 4.55 g of impure 8-bromo-3-(trifluoromethyl)quinoline and 3.89 g (37% yield) of 5-bromo-3-(trifluoromethyl)quinoline. Method [8] Retention time 6.75 and 7.47 min by HPLC (M+=276 and 278) and (M+=276 and 278).

Workup

  1. extractionextracted with methylene chloride
  2. dry with materialThe combined organic extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customchromatographed with 99:1, 49:1, 24:1, and 23:2 hexane

Sources & evidence

ORD record
ord-2e7e3e148aca4ae9a54f369622779e32
Source dataset
uspto-grants-2013_05
Patent number
US08450363B2

Reaction notes

Loading…